Wounds such as e.g. chronic wounds and ulcers affect nearly 1% of population and up to 10% of institutionalized patients. By the year 2030, 366 million people worldwide are estimated to suffer from diabetes further increasing the prevalence of chronic wounds and ulcers.
Aging population in the western world and increase in the prevalence of various diseases exposing to chronic wounds, such as diabetes and vascular diseases, have made it ever more important to develop novel therapeutic methods and further improve the existing therapeutic methods for non-healing ulcers. Social problems for an individual patient are enormous and the financial burden to the healthcare system is huge due to costly treatment of chronic wounds and the related indirect costs. To further underline the prevalent problem of chronic wounds and ulcers, in addition to increased mortality, approximately 80% of leg amputations are due to chronic vascular ulcers.
Lower extremity wounds of venous origin are commonly riddled with peripheral edema. This is due to vascular insufficiency; incompetence and dysfunction of veins and valves to transport blood in a normal way. This results in accumulation of highly conductive fluid into the interstitial space of the affected limb.
Edema prevents appropriate transport of oxygen and nutrients, which is essential for proper wound healing to occur. Edema also adds the mechanical stress in the wound site and disturbs waste removal from the wound area. A commonly used method to ease edema is compression therapy. Compression stockings are used for improving healing of chronic wounds of vascular etiology.
In summary, conventional treatment of chronic wounds and ulcers has so far been mainly passive; firstly to remove or control the impediments for healing and secondly to cover the wound area with an occlusive dressing to allow nature to take its course.
A finding in the wound care practices was that a moist environment is beneficial to the non-healing wound and that the occlusive dressings do not increase the risk for infection. This may partly relate to the improved ion transport and improved function of endogenous electric fields. Therefore, an ideal dressing for a chronic ulcer would provide a moist environment, absorb exudates, prevent the maceration of surrounding tissue and would be long term and cost effective. For wounds and ulcers that fail to heal, the treatment in the end often leads to surgical debridement under anaesthesia.
Recent studies suggest that endogenous electrical fields generated immediately after skin break may work as an initiating force for wound healing. This is due to instant collapse of transepithelial potential (TEP) in the wound area and resulting short circuit and flow of ionic current. As the wound heals the integrity of skin is gradually regained and eventually TEP is resumed.
Therefore, in order to improve the healing rate, a therapeutic approach which utilizes electrical stimulation of the wound via application of direct current should be beneficial. In a typical electrical stimulation of the wound low current and low voltage direct current is applied to the surface of the wound in order to stimulate the healing of the wound.
The electrical stimulation of the wound has been found to affect the biological healing of the wound in the inflammation phase of the wound, in the proliferation phase of the wound and in the epithelisation phase of the wound. In the inflammation phase of the wound the electrical stimulation of the wound initiates the wound healing process, increases the blood circulation, promotes phagocytosis, improves tissue oxygen intake, reduces edema, stimulates fibroblasts and epithelial cells, stimulates DNA synthesis, calms the infection and dissolves the necrotic tissue. In the proliferation phase of the wound the electrical stimulation of the wound stimulates fibroblasts and epithelial cells, stimulates DNA synthesis and protein synthesis, adenosine triphosphate (ATP) formation, enhances membrane transport and stimulates the diminishing of the wound. In the epithelisation phase of the wound the electrical stimulation of the wound stimulates the reformation and the migration of the epithelial cells and leads to softer and thinner skin, and improved scarring. Higher quality scarring is a factor in decreasing the high recurring tendency of a chronic wound.
Vascularization plays a role in soft tissue healing, and hence enhancing angiogenesis to ensure sufficient blood flow in the newly formed epithelial layer will support the healing process. Vascular endothelial growth factor (VEGF) has been successfully used in preclinical ischaemic tissue models to enhance and promote the development of collateral blood vessels. Also, dissolution of certain bioactive glass compositions have been shown to stimulate release of angiogenetic growth factors resulting in an in-crease in tubule branching and formation of complex networks of interconnected tubules. Soluble products of these bioactive glasses induce endothelial cell proliferation and up-regulation of VEGF production, which indicate that these glasses possess a proangiogenic potential. Significantly enhanced mitogenic stimulation of endothelial cells with an additive effect with VEGF release has also been observed in the presence of a BAG coating.
It has been shown that the applying of electrical stimulation in the form of low intensity direct current (LIDC) to the wound has caused the wound to heal drastically faster and at a wider area. The faster healing of the chronic wounds and ulcers brings substantial savings both in terms of financial costs and human suffering. Chronic wounds are a cause for disability, pain, emotional and social problems for the patients. Chronic wounds are associated with prolonged hospitalizations and considerable morbidity. These wounds, also known as ulcers, represent a major burden for the healthcare system affecting a large population of patients. Chronic wounds persist for months or even years representing medical, social, and economic problems for individuals and the society.
There are some prior art accelerating wound healing products in the market available as consumer products. However, the functionality of these prior art wound healing products is very limited as their principle of operation is based on a large number of independent miniature galvanic cells that are in contact with the wound area. Although this allows for easy adjustment of dressing size, the lack of possibility for controlling the current-flow, both in terms of magnitude and direction, is expected to diminish the effect of this therapy. The problem is that the stimulus current generated by this type of prior art electrode array does not penetrate into the actual wound tissue, but rather mainly flows along the wound surface which severely limits the accelerating effect on the healing process.
Furthermore, one major problem in wound care is associated with monitoring of the healing process. Today, the assessment of progress of chronic wound healing is generally based on visual investigation by photographing and monitoring the size and the colour of the wound. Visual assessment is always influenced by a certain degree of subjectivity. Sometimes ultrasound is used for imaging the structure of the wound; also laboratory tests of exudate samples or biopsied tissue are done. These methods are fairly laborious and cannot be applied for daily assessment of wound healing. All these methods require disturbing the wound by removal of the wound dressing and visual inspection of the wound area to assess the onset of formation of granulation tissue and to ensure that the wound is not becoming infected.
There are some prior art wound monitoring sensors available, e.g. array sensors which take the form of patterns on insulating material. However, these prior art wound monitoring sensors may typically use materials that interfere with or irritate the wound, occlude the wound and can cause skin maceration. Also, some of the prior art wound monitoring sensors adhere to the wound, which can result in wound damage when they are removed. Furthermore, some of the prior art wound monitoring sensors also interfere with the healing of the wound by interfering with moisture control, whilst some only have a limited lifetime in a wound environment.
As the bioimpedance measurement utilizes low level AC excitation current, it does not possess any risks or inconvenience for the patient. The idea of utilizing bioimpedance monitoring of a chronic wound is based on the pathophysiology of the wound. Often the integrity of the skin is lost in chronic wounds, and from an electrical point of view, the loss of high impedance stratum corneum leads into steep decrease in measured impedance. As the healing of the wound proceeds, the wound base lifts up and the wound starts to close up from the peripherals. Finally, the skin integrity is obtained. The gradual gain in the skin integrity is observed as increasing impedance particularly at lower frequencies.
Generally speaking, a chronic wound is trapped in an on-going inflammation phase of the wound healing process. Prolonged inflammation of a chronic wound is characterized by accumulation of highly conductive fluid into the wound and the surrounding area. The fluids may accumulate into the intracellular space as a result of ischemia. If the blood flow to the tissues is interrupted, cell metabolism continues but in an anaerobic way. However, a prolonged ischemia inevitably results in decline of metabolism. This results in the decreased activity of ion pumps, which leads changes in the ion distribution in extracellular fluid and intracellular fluid. The result is cellular edema because of inflow of water and sodium into the cell. The decline of extracellular fluid volume reduces the width of the electrical path of the low frequency current and increases the extracellular resistance. Severe ischemia finally results in cell necrosis. The cellular integrity is lost in necrosis and intracellular fluid leaks into the extracellular space. The necrosis is observed as a decrease in extracellular resistance.
The fluids in a chronic wound may also accumulate into extracellular space. The increased volume of extracellular fluid can be observed as a decrease in the extracellular resistance. Often related to the chronic wounds, the swelling is due to increased vasodilatation and increased permeability of the capillaries. As a result of this the fluid accumulates into the extracellular space. Another possible cause for fluid accumulation is peripheral edema. Peripheral edema results from increased capillary permeability or impaired return of fluid by lymphatic system from the interstitial space to vascular compartment. Lymphedema is a result of impaired function of lymphatic system and the fluid tends to accumulate into the extracellular space.
European patent specification EP 1569553B1 presents a prior art wound mapping system presenting an array of rectangular electrodes that may be used to stimulate wound tissue electrically or measure impedance of wound tissue. The measurement electrodes are isolated from each other by a non-conducting hydrogel layer. In use, the conducting parts of the stimulating electrodes are in direct contact with wound tissue via a hydrogel patch on the exposed conducting electrode. The conducting parts of the stimulating electrodes are designed to be electrically connected to the tissue but not to measure moisture above the wound or at a localised site between the electrodes. However, this allows the electrodes to dry into healing tissue and stick to the healed cell layer. Removal of the device with the wound dressing would remove the healed skin. Application of a hydrogel to the electrodes in contact with the wound area does little to alleviate the problem as it will dry out before removal of the dressing. Development of a tool that would allow objective online monitoring without disturbance would be of great importance.
Conventional prior art wound dressings and prior art electrode arrangements for facilitating wound healing have many problems and disadvantages. Regardless of the massive effort put into and improvements obtained in the area of the treatment of chronic wounds, many chronic wounds still remain non-responsive to the conventional treatment and a need to further develop the existing and new therapeutic methods is obvious. Furthermore, the need for continuous, non-invasive and objective solution for monitoring chronic wound healing without disturbing the delicate healing process is also obvious.
As mentioned above, there are a lot of deficiencies in the current wound dressings and electrode arrangements for facilitating wound healing. There is a clear demand in the market for a new type of an electrode arrangement for facilitating wound healing that would be better and more efficient than the current prior art electrode arrangement solutions. Likewise, there is a clear demand in the market for a new type of a wound dressing having a wound healing electrode arrangement that would be better and more efficient than the current prior art wound dressing solutions.